NVS-SM1, SMN2 Splicing Modulator


Catalog No. size PriceQuantity
M60277-2S 2 mg solid $129
M60277-C CUSTOMER ORDER $9,999Unavailable

Description

Product Information

Molecular Weight: 393.49
Formula: C22H27N5O2
Purity: ≥98%
CAS#: n/a
Solubility: DMSO up to 100 mM
Chemical Name: Chemical Name: 5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenol
Storage: Powder: 4oC 1 year. DMSO: 4oC 3 month; -20oC 1 year.

 

Biological Activity:

NVS-SM1 is a highly potent, selective and orally active small molecule SMN2 splicing modulator enhancing SMN exon 7 inclusion with EC50 ~20 nM. It elevates full-length SMN protein and extends survival in a severe Spinal Muscular Atrophy (SMA) mouse model. The molecular mechanism of action for NVS-SM1 is via stabilization of the transient double-strand RNA structure formed by the SMN2 pre-mRNA and U1 small nuclear ribonucleic protein (snRNP) complex. The binding affinity of U1 snRNP to the 5' splice site is increased in a sequence-selective manner, discrete from constitutive recognition. This new mechanism demonstrates the feasibility of small molecule-mediated, sequence-selective splice modulation and the potential for leveraging this strategy in other splicing diseases. Currently NVS-SM1 is in phase I clinical trial for treatment of type I SMA

How to Use:

In vitro: NVS-SM1 was used at 0.1-1 µM final concentration in vitro and in cellular assays. 

In vivo: NVS-SM1 was dose to C/+ SMA mouse model by oral administration at 1-3 mg/kg once per day. 

References: 

  • 1. Palacino J, et al. SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice. (2015) Nat Chem Biol. 11(7):511-7.


 

Products are for research use only. Not for human use.

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